Variant 19-50856310-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001648.2(KLK3):c.117G>A(p.Gln39Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,613,514 control chromosomes in the GnomAD database, including 1,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.066 ( 805 hom., cov: 31)

Exomes 𝑓: 0.021 ( 880 hom. )

Consequence

KLK3
NM_001648.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

KLK3 (HGNC:6364): (kallikrein related peptidase 3) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

KLK3 links:

KLK3 (HGNC:):

KLK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.697578).

BP6

Variant 19-50856310-G-A is Benign according to our data. Variant chr19-50856310-G-A is described in ClinVar as [Benign]. Clinvar id is 3056767.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2 linkuse as main transcript	c.117G>A	p.Gln39Gln	synonymous_variant	2/5	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 linkuse as main transcript	c.117G>A	p.Gln39Gln	synonymous_variant	2/5		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 linkuse as main transcript	c.117G>A	p.Gln39Gln	synonymous_variant	2/5		NP_001025219.1	P07288-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.117G>A	p.Gln39Gln	synonymous_variant	2/5	1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.0661

AC:

10057

AN:

152136

Hom.:

805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0269

AC:

6749

AN:

251352

Hom.:

342

AF XY:

0.0231

AC XY:

3141

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.0342

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0204

GnomAD4 exome

AF:

0.0208

AC:

30410

AN:

1461260

Hom.:

880

Cov.:

AF XY:

0.0196

AC XY:

14242

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.0331

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0662

AC:

10072

AN:

152254

Hom.:

805

Cov.:

AF XY:

0.0660

AC XY:

4910

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0379

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.0510

Alfa

AF:

0.0355

Hom.:

153

Bravo

AF:

0.0711

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.182

AC:

802

ESP6500EA

AF:

0.0178

AC:

153

ExAC

AF:

0.0303

AC:

3683

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0145

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KLK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.33

FATHMM_MKL

Benign

0.56

GERP RS

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over